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Notes: Cough variant asthma is an occult form of asthma in which the only sign or symptom is chronic cough. It is a common problem amongst all ages that frequently goes unrecognized, leading to under diagnosis and under treatment. To characterize the pathophysiological abnormalities in these patients, we performed bronchial provocation tests with methacholine using the stepwise doubling concentration technique, and measured the concentration of methacholine and the severity of airway obstruction when wheezing was first detected. Airway hyper responsiveness, defined as PC20 in the cough variant asthma group was not significantly different from that of classic asthma. There was a good correlation between the PCW (the concentration of methacholine causing wheezing) and the PC20 with the PCW values higher than PC20 values in both groups. However, in the cough variant asthma group, the PCW: PC20 ratio was greater than that of the classic asthma group. Furthermore, the mean % fall in FEV1 at which wheezing was first detected in the former group was significantly larger than that of the latter group. The results indicated that the mechanism for the manifestation of cough without wheeze in the cough variant asthma may be a higher wheezing threshold, i.e. wheezing becomes audible at the greater degree of airway obstruction than classic asthma. They suggested that patients with cough variant asthma may represent a subset of asthmatic subjects whose airways are less able to produce a wheeze.

Notes: Background Recent investigation has revealed that spider mites such as Tetranychus urticae and Panonychus ulmi are important allergens in the development of occupational asthma among apple farmers.Objective To evaluate IgE binding components in T. urticae and P. ulmi-derived crude extracts and their cross-reactivity with Panonychus citri, Tyrophagus putrescentiae and Dermatophagoides pteronyssinus in apple cultivating farmers.Methods Thirty-one apple farmers with positive skin responses to T. urticae or P. ulmi were randomly recruited, and specific IgE levels in their sera were measured using ELISA. Cross-reactivity was evaluated by ELISA inhibition. IgE binding components were evaluated by IgE immunoblotting.Results A total of 11 IgE binding components in T. urticae and 10 in P. ulmi were found. Among them, the 17 kDa, 27 kDa, 33 kDa, 37 kDa, 41 kDa, 56 kDa, and 75 kDa allergens in T. urticae, and the 33 kDa, 41 kDa, and 51 kDa allergens in P. ulmi were identified as dominant allergens. T. urticae-specific IgE binding was completely inhibited by 100 μg/mL of T. urticae (99.7%), but only partially inhibited by P. citri (83.0%), P. ulmi (71.6%), T. putrescentiae (69.7%), and D. pternonyssinus (60.1%). P. ulmi-specific IgE binding was completely inhibited by additions of P. citri (92.3%) and P. ulmi (91.2%), but only partially inhibited by the addition of T. urticae (61.5%), T. putrescentiae (57.7%), and D. pteronyssinus (54.4%).Conclusion There were seven dominant allergens found in T. urticae and three in P. ulmi. T. urticae- and P. ulmi-specific IgE bindings were partially inhibited by crude extracts derived from D. pteronyssinus and T. putrescentiae.

Notes: Background Recent investigations have demonstrated that the citrus red mite (Panonychus citri, CRM) is the most important allergen in citrus fruit farmers with asthma and rhinitis and a common sensitizing allergen in children living near citrus orchards.Objective To evaluate the sensitization rate to CRM and the association between sensitization to CRM and atopic diseases, such as athma, allergic rhinitis and atopic dermatitis, in adolescents living in rural areas with citrus orchards.Methods A total of 2005 adolescents (aged from 16 to 18 years) living in rural areas with citrus orchards were enrolled. Subjects were evaluated by a questionnaire and a skin prick test with 11 common aeroallergens including CRM.Results The prevalences of current wheeze, rhinoconjuntivitis, and eczema on the questionnaire were 13.0%, 13.6%, and 8.8%, respectively. On skin prick tests, the most common sensitizing allergen was CRM [20.6%], followed by Dermatophagoides pteronyssinus (18.5%), D. farinae (14.6%) and cockroach (9.8%). The prevalence of current eczema was significantly associated with the sensitization to CRM (OR = 1.9, 95% CI 1.3–2.9), although the prevalence of current wheeze and rhinoconjunctivitis was not associated with it. Among adolescents living near citrus orchards, however, the prevalences of current wheeze and rhinoconjuncitivitis were significantly higher in those with sensitization to only CRM than in those without sensitization to any allergens (20.3% vs. 14.1% and 20.3% vs. 15.0%, P 〈 0.05, respectively).Conclusion CRM is the most common sensitizing allergen in adolescents living in rural areas with citrus orchards, and sensitization to CRM was significantly associated with the prevalence of atopic dermatitis.

Notes: Specific IgE responses to allergens provide useful models for evaluating the genetic factors that control human immune responses. A recent survey demonstrated that the citrus red mite (Panonychus citri, CRM) is the most important allergen in the development of asthma in citrus farmers.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectiveThe aim of this study was to evaluate whether susceptibility or resistance to CRM-induced asthma was associated with HLA-DRB1 gene.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsDNAs were extracted from two groups of unrelated Korean adults living around citrus farms: (1) Ninety-one adults with CRM-sensitive asthma; and (2) 98 exposed, healthy nonatopic controls. Genotypes of HLA-DRB1 alleles were carried out using PCR-based methods.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsAllelic frequency of HLA-DRB1*07 was higher in the CRM-sensitive asthmatics compared to the controls (17.6% vs 4.1%, Pc = 0.01). Conversely, the frequency of DRB1*04 was lower in the CRM-sensitive asthmatics compared to the controls (19.8% vs 40.8%, Pc = 0.01). No significant difference was found in the distributions of the other HLA-DRB1 gene-encoded antigens between the two groups.〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionHLA-DRB1 genes may be involved in the development of CRM-induced asthma. In addition, HLA-DR7 may increase, and DR4 decrease, the risk of developing the asthma in CRM-exposed adults.

Notes: Background With β-agonists being the most widely used agents in the treatment of asthma, in vitro studies reported that β2-adrenergic receptor (ADRB2) polymorphisms are associated with agonist-promoted down-regulation.Objective The present population-based study aimed to evaluate the association between bronchodilating response to inhaled short-acting β-agonist and two non-synonymous single-nucleotide polymorphisms (SNPs) of ADRB2 (ADRB2-16 and ADRB2-27).Methods Two hundred and nine children with reduction in forced expiratory volume in 1 s of more than 20% on methacholine bronchial challenge underwent bronchodilating response testing 5 min after the inhalation of 200 μg of albuterol. Of these 209, 195 gave peripheral blood for genotyping of ADRB2 polymorphisms.Results The bronchodilating response was significantly higher in subjects with the homozygous Arg16 than in those with the homozygous Gly16. It was further demonstrated that haplotype pairs of the homozygous Arg16Gln27 and of the heterozygous Arg16Gln27/Gly16Glu27 showed the highest bronchodilating responses, and the haplotype pairs of the homozygous Gly16Gln27 the lowest response. As a whole, the bronchodilating response was more positively associated with the combined quantity of Arg16 and Glu27 polymorphisms than with that of Arg16 alone.Conclusion Non-synonymous SNPs of ADRB2 at codons 16 and 27 is significantly associated with bronchodilating response to inhaled short acting β-agonists.

Notes: Background  Our previous work on linkage analysis showed that histamine release from basophils to anti-IgE stimuli was linked to the gene marker of chromosome 11q13, where the β chain of the high-affinity receptor for IgE (FcεRI-β) is located.Objective  To evaluate the association between FcεRI-mediated histamine release from basophils and four bi-allelic single nucleotide polymorphisms of the FcεRI-β gene.Methods  Phenotypes of asthma, such as maximal histamine release from basophils and atopy, were measured from 80 randomly recruited asthmatic children. Polymorphisms of the FcεRI-β gene were determined by PCR-based methods.Results  The polymorphism in exon 7, resulting in Glu to Gly substitution, was significantly associated with histamine release from basophils to anti-IgE stimuli, but not with total IgE levels and skin test responses to aeroallergens.Conclusion This study supports a role for the FcεRI-β gene in the expression of high affinity IgE receptor-mediated histamine release from basophils.

Notes: There have been few reported cases of occupational asthma induced by Pinellia ternata (Banha), and the mechanism responsible for this type of asthma is still undetermined. We report a case of Banha-induced occupational asthma with IgE-mediated mechanism. The patient had positive skin responses to Banha extract and Banha-specific bronchial challenge elicited an early asthmatic response. The serum-specific IgE binding to Banha extract was detectable and completely inhibited with the additions of 0.1 µg/mL of Banha extract on ELISA inhibition. Seven IgE binding components to Banha extract (6.5, 22, 24, 32, 34, and 48 kDa) were detected using SDS–PAGE and immunoblot analysis. In conclusion, the results of this study suggest that P. ternata (Banha)-derived allergens are able to cause IgE-mediated bronchoconstriction in exposed workers.

Notes: Background In most epidemiological survey studies, only subjective symptoms and past medical history of asthma have been used as diagnostic criteria. Even though a questionnaire survey can be performed in a large population study at low cost, limitations such as lack of objectivity and poor predictability in non-specific bronchial hyperresponsiveness cannot be avoided.Objectives The purpose of this study was to elucidate the prevalence of current asthma based on questionnaires and methacholine bronchial provocation test, and the prevalence of atopy in Korea.Methods We performed modified ATS respiratory questionnaires and allergen skin-prick test with 10 common inhalant allergens among 3219 subjects aged 7–19 years in Seoul and a rural part of a small city, Chungju in Korea. Methacholine bronchial provocation tests were also performed among those who had asthma symptoms according to the questionnaire. The criteria of asthma was presence of both asthma symptoms and non-specific bronchial hyperresponsiveness. Atopy was defined as when an allergen induced weal size is same or larger than that caused by histamine.Results The prevalence of asthma based on questionnaires and methacholine bronchial provocation tests was 4.6%, while the prevalence of wheeze was 8.2% and 19.3% of total population complained of one or more respiratory symptoms related to asthma on the questionnaires. There was no significant difference according to age, sex and living area. The mean prevalence of atopy was 35.0% and the most common allergens were Dermatophagoides farinae (30.9%), Dermatophagoides pteronyssinus (27.5%), cat fur (20.4%) and cockroach (11.8%). The atopy prevalence in Chungju area was higher than that in Seoul and males showed a higher prevalence than females. The asthma prevalence was higher among atopies (6.8%) than among non-atopies (2.7%). None of questionnaire items were enough to predict the presence of bronchial hyperresponsiveness in terms of sensitivity, specificity and positive predictive value.Conclusion The prevalence rate of current asthma in Korea was 4.6% and the prevalence rate of atopy in Korea was 35.0%. Questionnaire-based surveys are not enough to predict the actual prevalence of asthma.

Notes: Background Allergen-specific immunotherapy has proven to be clinically effective in the treatment of patients with atopic asthma; however, the mechanisms are still unclear. Several noted immunological changes include an increase of the allergen-specific IgG antibody, a reduction in the allergen-specific IgE antibody subsequent to transient increase, an allergen-specific T cell shift in cytokine production from Th2 to Th1, and a decrease in quantity and activity of basophils and mast cells.Objective To analyse the changes of basophil histamine release in response to IgE-mediated and non-IgE-mediated stimuli before and after conventional house-dust mite immunotherapy in children who suffer from atopic asthma.Methods Fourteen Dermatophagoides farinae (Df) sensitive asthmatic children with conventional immunotherapy were examined. Basophil histamine releasability was measured 0 months (just before immunotherapy), 4 months and 9 months after immunotherapy. Basophils were stimulated with Df and goat anti-human IgE antibody as IgE-mediated stimuli; and formyl-Met-Leu-Phe (fMLP) and calcium ionophore A23187 as non-IgE-mediated stimuli. Accordingly, the asthma symptom score was used to assess clinical outcome and the skin test reactivity to Df was measured.Results In contrast to pre-immunotherapy activity, 4 and 9 months after immunotherapy there were significant decreases in histamine release by Df and by anti-IgE antibody. The histamine release by fMLP and by calcium ionophore showed no significant changes after immunotherapy. Histamine release by Df demonstrated significant correlation to that by anti-IgE antibody and by fMLP, yet there was no observable correlation between histamine release by Df and by calcium ionophore. The asthma symptom score decreased significantly 4 and 9 months after immunotherapy and showed significant correlation with histamine release by Df. The skin test reactivity (allergen/histamine ratio) remained constant 4 months after immunotherapy, but decreased significantly 9 months after immunotherapy.Conclusion Basophils have the potential to play an important role in the early clinical improvement of conventional immunotherapy in children with atopic asthma, which may be a result of the decreased IgE-mediated histamine releasability during immunotherapy.